Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

HIV Infections Clinical Trial

Official title:

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Atripla® (Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00869557
• Other study ID #: GS-US-236-0104
• Status: Completed
• Phase: Phase 2
• First received: March 24, 2009
• Last updated: May 22, 2014
• Start date: April 2009
• Est. completion date: September 2013

Study information

• Verified date: May 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objective of this double-blinded, multicenter, randomized, active-controlled study is to evaluate the safety and efficacy of Stribild, a single-tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adult participants. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs.

Participants will be randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded (Week 60), at which point all participants will attend an Unblinding Visit and be given the option to participate in an open-label rollover extension (the extension is scheduled to be open until Stribild becomes commercially available, or until Gilead Sciences elects to terminate the study).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: September 2013
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Plasma HIV-1 RNA levels = 5,000 copies/mL

• No prior use of any approved or experimental anti-HIV drug

• Normal electrocardiogram (ECG)

• Adequate renal function: estimated glomerular filtration rate = 80 mL/min according to the Cockcroft-Gault formula

• Hepatic transaminases = 2.5 x upper limit of normal (ULN)

• Total bilirubin = 1.5 mg/dL, or normal direct bilirubin

• Adequate hematologic function

• Cluster determinant 4 (CD4) cell count > 50 cells/µL

• Serum amylase = 1.5 x ULN

• Normal thyroid-stimulating hormone

• Negative serum pregnancy test (for females of childbearing potential only)

• Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drugs

• Life expectancy = 1 year

• Ability to understand and sign a written informed consent form

Exclusion Criteria:

• New acquired immunodeficiency syndrome (AIDS)-defining condition diagnosed within the 30 days prior to screening

• Documented drug resistance to nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitors or primary protease inhibitor resistance mutation(s)

• Hepatitis B surface antigen positive

• Hepatitis C antibody positive

• Participants experiencing cirrhosis

• Participants experiencing ascites

• Participants experiencing encephalopathy

• Females who are breastfeeding

• Positive serum pregnancy test (for females of childbearing potential)

• Vaccinated within 90 days of study dosing

• History or family history of Long QT Syndrome or family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30

• Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities

• Prolonged QTcF interval at screening

• PR interval = 200 msec or = 120 msec on ECG at screening

• QRS = 120 msec on ECG at screening

• Implanted defibrillator or pacemaker

• Participants receiving ongoing therapy with any disallowed medications

• Current alcohol or substance use judged to potentially interfere with participant study compliance

• History of or ongoing malignancy (including untreated carcinoma in situ) other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma

• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline

• Participation in any other clinical trial without prior approval

• Medications contraindicated for use with EFV, EVG, COBI, FTC, or TDF

• Any known allergies to the excipients of Atripla or Stribild tablets

• Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV
• HIV Infections

Intervention

Drug:
• Stribild
Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily (QD) + placebo to match Atripla once daily prior to bedtime (QHS)
• Atripla
Atripla (EFV 150 mg/FTC 200mg/TDF 300 mg) STR QHS + placebo to match Stribild QD

Locations

Country	Name	City	State
United States	Chase Brexton Health Services, Inc.	Baltimore	Maryland
United States	Be Well Medical Center	Berkley	Michigan
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Northstar Medical Center	Chicago	Illinois
United States	AIDS Arms/ Peabody Health Center	Dallas	Texas
United States	Nicholaos Bellos, MD, PA	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta (IDSA)	Decatur	Georgia
United States	Apex Research Institute	Denver	Colorado
United States	Broward Health	Fort Lauderdale	Florida
United States	Gary Richmond, MD, PA, Inc.	Fort Lauderdale	Florida
United States	Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	Health for Life Clinic, PLLC	Little Rock	Arkansas
United States	The Living Hope Foundation	Long Beach	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	Chelsea Village Medical	New York	New York
United States	Ricky K. Hsu, MD, PC	New York	New York
United States	Orange Coast Medical Group	Newport Beach	California
United States	East Bay AIDS Center	Oakland	California
United States	Infectious Disease of Central Florida	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Metropolis Medical	San Francisco	California
United States	Southwest C.A.R.E. Center	Santa Fe	New Mexico
United States	TribalMed	Seattle	Washington
United States	Southampton Healthcare, Inc.	St. Louis	Missouri
United States	Treasure Coast Infectious Disease Consultants	Vero Beach	Florida
United States	Capital Medical Associates PC	Washington	District of Columbia
United States	Dupont Circle Physicians Group	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

Cohen C, Elion R, Ruane P, Shamblaw D, DeJesus E, Rashbaum B, Chuck SL, Yale K, Liu HC, Warren DR, Ramanathan S, Kearney BP. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate v — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24	The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.	Week 24	No
Secondary	The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48	The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.	Week 48	No
Secondary	Change From Baseline in HIV-1 RNA (log_10 Copies/mL)	Change = Week 24 or 48 value minus baseline value	Baseline to Weeks 24 and 48	No
Secondary	Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24	Change = Week 24 value minus baseline value	Baseline to Week 24	No
Secondary	Change From Baseline in CD4 Cell Count at Week 48	Change = Week 48 value minus baseline value	Baseline to Week 48	No
Secondary	The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL	The percentage of participants with virologic success at Weeks 24 and 48 assessed using the FDA-defined snapshot analysis for an HIV-1 RNA cutoff of 50 copies/mL was summarized.	Baseline to Weeks 24 and 48	No

External Links

•   Gilead Sciences